1. Field of the Invention
This invention relates to novel 4-substituted isoquinolone derivatives possessing excellent inhibitory action for 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase, and their production and use.
The compounds of this invention can inhibit the activity of HMG-CoA reductase which is a limiting enzyme for the biosynthesis of cholesterol and then control said biosynthesis of cholesterol, and accordingly are useful as a drug for preventing and/or treating hypercholesterolemia, atherosclerosis related thereto and various diseases caused thereby (e.g., ischemic cardiac diseases such as myocardial infarction, cerebrovascular disturbances such as cerebral infarction, cerebral apoplexy, etc.).
2. Description of the Prior Art
Some lactone derivatives isolated from bacteria or fungi fermentation broths, such as compactin, mevinolin and CS-514 are known as an inhibitor for HMG-CoA reductase [A. Endo, J. Med. Chem. 28, 401 (1985)]. Recently, other synthesized compounds possessing HMG-CoA reductase inhibitory activity, e.g., 3,5-dihydroxy-6-heptenoic (or heptanoic) acids substituted with 6-membered heterocyclic groups at the 7 position have been disclosed in U.S. Pat. No. 4,761,419 (of those substituted with quinoline), European Patent Application Nos. 307,342A and 306,929A (those with pyridine), European Patent Application No. 324347A (those with pyridazine) and European Patent Application No. 308,736A (those with pyrimidine). However, neither chemical synthesis nor HMG-CoA reductase inhibitory activity on isoquinolone compounds substituted with a 3,5-dihydroxy-6-heptenoic (or heptanoic) acid group at the 4 position are reported heretofore.